Calcitonin receptors were found in uniquely high concentrations in the periaqueductal gray matter (PAG) of the rat. Injections of calcitonin into this region produced profound analgesia. Iontophoretic applications of neurotensin to PAG neurons increased their firing rate. Injections of neurotensin into the PAG also increased the firing rate of raphe magnus neurons, indicating an activation of descending inhibitory mechanisms. Injections of neurotensin into the substantia nigra and caudate nucleus increased dopamine metabolites in these structures without increasing release. Choleccystokinin receptors were found to be localized on intrinsic non-dopaminergic cell bodies in the striatum and substantia nigra. Employing the new in vivo autoradiographic procedures, this was found to increase release of endorphins in the PAG, hypothalamus, midline thalamic structures and reticular formation. Employing local cerebral glucose utilization (LCGU) procedures, rewarding brain stimulation of the ventral tegmental area was found to increase glucose consumption in a highly circumscribed zone that extended both laterally and caudally through the medial forebrain bundle, extending via the diagnonal band of Broca to the level of the pre-optic area. LCGU procedures also revealed that nigral dopamine neurons are essential for metabolic activation of the entopeduncular and subthalamic nuclei in nigral stimulated rats. Opiate receptors, with a mu ligand selectivity pattern, showed striking laminar heterogeneity in rat cortex and were densest in limbic cortical areas.